Gastrointestinal stromal tumors (GISTs) are the most common mesenlalymal neoplasms UI lne intestinal tract. Surgery has been the only effective therapy for GIST. However, the majority of the patients eventually die from recurrent disease despite complete removal of their primary tumor. Nearly all GISTs express Kit protein (stem cell factor receptor), a type III receptor tyrosine kinase that is implicated in cell growth and survival. Most GISTs have a gain of function mutation in the c-kit proto-oncogene that results in ligand-independent activation of Kit. ST1571 is a small molecule that selectively inhibits Kit. Its use marks a new era of rational and targeted molecular inhibition of cancer. ST1571 is the most active agent for GIST to date with partial response rates exceeding 50% in a CTEP sponsored Phase II trial of patients with metastatic GIST. ST1571 may prove even more effective in treating occult microscopic disease following the surgical resection of primary GISTs. A CTEP-sponsored, multicenter, American College of Surgeons Oncology Group (ACOSOG) Phase 11 trial will test the benefit of adjuvant ST1571 in patients with a completely resected, high risk, primary GIST. Tissue specimens from patients enrolled on this initial ACOSOG study will be analyzed in this proposal. The long-term hypothesis is that the tumor phenotype and genotype will account for the individual differences in ST1571 response and therefore survival. The specific aims of this proposal are to: 1) characterize the morphologic and immunohistochemical phenotype of primary GIST, 2) determine the c-kit gene mutation status of primary GIST, 3) define the cytogenetic profile of primary GIST, and 4) establish a database that will permit future correlation of primary GIST features to clinical outcome following ST1571 therapy. This study will be the first prospective analysis of primary GISTs and it will be based upon the first adjuvant study using STI571. The results are essential to advance our understanding of GIST biology and determine the therapeutic value and limitations of STI571.